Abstract
BackgroundExtracellular matrix remodelling regulated by matrix-metalloproteinase (MMP) inducer (CD147) is a crucial process during tumor cell invasion and regulation of blood supply. In this study, we evaluated the correlation of CD147 and MMP-2 expression with major prognostic factors for uveal melanoma and the development of metastasis.MethodsThe expression of CD147 and MMP-2 was analyzed in 49 samples of uveal melanomas. Triple immunofluorescence stainings using markers against glial cells (GFAP), endothelial cells (CD34) and macrophages (CD68) were performed to further analyse the exact localisation of CD147 and MMP-2 positivity. In 28 cases clinical metastatic disease were found. The remaining 21 cases showed no signs of metastatic disease for an average follow-up of 10 years. Correlation analysis (Pearson correlation) was performed to analyse the association of CD147 and MMP-2 expression with known prognostic factors, vasculogenic mimicry (VM), the mature vasculature (von Willebrand Factor) and tumor induced angiogenesis (by means of Endoglin expression).ResultsCD147 and MMP-2 were expressed in 47 (96.0 %) of the uveal melanomas. CD147 up-regulation was significantly correlated with a higher MMP-2 expression. The overall expression analysis revealed no significant difference in the metastatic (p = 0.777) and non-metastatic subgroup (p = 0.585). No correlation of CD147 expression and any system of blood supply was evident. In the non-metastatic sub-group a significant correlation of clustered CD147 positive cells with largest basal diameter (p = 0.039), height (p = 0.047) and TNM-stage (p = 0.013) was evident.ConclusionsThese data may indicate that CD147 regulates MMP-2 expression in uveal melanoma cells.
Highlights
Extracellular matrix remodelling regulated by matrix-metalloproteinase (MMP) inducer (CD147) is a crucial process during tumor cell invasion and regulation of blood supply
Tumor growth is dependent on the blood supply, which is delivered on the one hand by angiogenesis
In the primary tumor a weak colocalisation of matrixmetalloproteinase inducer (CD147) and matrix metalloproteinases (MMPs)-2 was observed in some CD68 positive cells, which were probably tumor-infiltrating macrophages (Fig. 3c)
Summary
Extracellular matrix remodelling regulated by matrix-metalloproteinase (MMP) inducer (CD147) is a crucial process during tumor cell invasion and regulation of blood supply. Tumor growth is dependent on the blood supply, which is delivered on the one hand by angiogenesis. Angiogenesis includes the outgrowth and proliferation of endothelial cells that remodel the extracellular matrix and align into tube-like structures, and eventually form functional blood vessels. During angiogenesis and vasculogenic mimicry extracellular matrix remodelling is a crucial process. It involves numerous extracellular matrices – degrading enzymes including matrix metalloproteinases (MMPs), which are believed to affect tumor angiogenesis and VM and tumor growth, local invasion, and subsequent distant metastasis [2, 3].
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